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Major gene study uncovers secrets of leukemia

Investigators at St. Jude Children's Research Hospital have discovered previously unsuspected mutations that contribute to the formation of pediatric acute lymphoblastic leukemia (ALL), the most common cancer in children. The discovery not only suggests novel methods for treating pediatric ALL, but also provides a roadmap for the identification of unsuspected mutations in adult cancers.

ALL is a tumor in which immature white blood cells that normally develop into immune system cells, called B or T lymphocytes, instead multiply rapidly and overwhelm the normal blood cells the body needs to survive.

The St. Jude team used microarrays, postage-stamp-sized chips that contain DNA fragments, which allowed researchers to investigate more than 350,000 markers called single nucleotide polymorphisms. Single nucleotide polymorphisms are individual variations in the DNA that are spaced across the human chromosomes. Single nucleotide polymorphisms function as flags for researchers, allowing them to detect specific deletions of DNA in a gene or increases in the number of specific genes at a level of detail that was previously unattainable. The St. Jude group used this approach to analyze leukemia samples from 242 pediatric patients with ALL. This identified an unexpectedly high frequency of mutations involving genes that function as master regulators of normal B-cell development and differentiation.

A report on this work appears in the March 7 online edition of "Nature."

"The results of our study demonstrate that it is possible to significantly speed the identification of the genetic lesions that are the underlying cause of not only ALL, but also many other cancers, including those affecting adults," said James Downing, M.D., scientific director and chair of the Pathology department at St. Jude. He is senior author of the paper.

The study found that 40 percent of patients with ALL had deletions or mutations in one of three so-
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Source:St. Jude Children's Research Hospital


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